Quinone methide

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A quinone methide is a type of conjugated organic compound that contain a cyclohexadiene with a carbonyl and an exocyclic methylene group or extended alkene unit. It is analogous to a quinone, but having one of the double bonded oxygens replaced with a carbon. The carbonyl and methylene are usually oriented either ortho or para to each other. There are some examples of transient synthetic meta quinone methides.

Tetracyanoquinodimethane is an organic oxidant.

A quinone dimethide is a related derivative in which both carbonyl groups of a quinone are replaced by methylene groups. A well studied example is tetracyanoquinodimethane.

Properties[edit]

Quinone methides are more polar than quinones, and therefore more chemically reactive in a variety of situations. Simple quinone methides are short lived reactive intermediates that are not stable enough to be isolated under normal circumstances but quickly react with nucleophiles and other reactants. Some quinone methides have structural (e.g. steric hindrance) or electronic characteristics that stabilize them enough to be isolated.

Occurrence and applications[edit]

Quinones methides and their derivatives are common constituents of biological systems. Quinone methanide itself arises by the degradation of tyrosine, leading ultimately to p-cresol.[1] Various quinone methides are directly involved in the process of lignification (creation of complex lignin polymers) in plants.[2]

Many quinone methides show pronounced biological activity. They have been implicated as the ultimate cytotoxins responsible for the effects of such agents as antitumor drugs, antibiotics, and DNA alkylators.[3] Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs.

Celastrol is a triterpenoid quinone methide isolated from Tripterygium wilfordii (Thunder of God vine) and Celastrus regelii that exhibits antioxidant (15 times the potency of α-tocopherol),[4] anti-inflammatory,[5] anticancer,[6][7][8][9] and insecticidal [10] activities.

Pristimerin, the methyl ester of celasterol, is a triterpenoid quinone methide isolated from Maytenus heterophylla that displays antitumor and antiviral [11] activities. Pristimerin has also been found to have a contraceptive effect due to its inhibiting effect on the calcium channel of sperm (CatSper).[12]

Maytenoquinone

Taxodone and its oxidized rearrangement product, taxodione, are diterpenoid quinone methides found in Taxodium distichum (bald cypress), Rosmarinus officinalis (rosemary), several Salvia species and other plants, that display anticancer,[13][14][15] antibacterial,[16][17][18] antioxidant,[19] antifungal,[20] insecticide,[21] and antifeedant [22] activities.

Maytenoquinone, an isomer of taxodione, is a biologically active quinone methide found in Maytenus dispermus.[23]

Kendomycin 2.png

Kendomycin is an antitumor antibacterial quinone methide macrolide first isolated from the bacterium Streptomyces violaceoruber.[24] It has potent activity as an endothelin receptor antagonist and anti-osteoporosis agent.[25]

Elansolid A3 is a quinone methide from the bacterium Chitinophaga sancti that displays antibiotic activity.[26] Antibacterial quinone methides, 20-epi-isoiguesterinol, 6-oxoisoiguesterin, isoiguesterin and isoiguesterinol were found in Salacia madagascariensis.[27] Quinone methides tingenone and netzahualcoyonol were isolated from Salacia petenensis.[28] Nortriterpenoid quinone methide amazoquinone and (7S, 8S)-7-hydroxy-7,8-dihydro-tingenone were isolated from Maytenus amazonica.[29] An antimicrobrial quinone methide, 15 alpha-hydroxypristimerin, was isolated from a South American medicinal plant, Maytenus scutioides.[30]

Preparation[edit]

Quinone methides are often prepared by oxidation of the corresponding ortho or para phenol toluene.

Quinone methides can be produced in aqueous solution by photochemical dehydration of o-hydroxybenzyl alcohols.

Reactions[edit]

Quinone methides are electrophilic Michael acceptors that generally react quickly with nucleophiles, other reactants, and are readily reduced. Quinone methides are conjugated but not aromatic. Conjugate addition usually breaks the conjugation. Reduction can either rearomatise the compound or break the conjugation.

References[edit]

  1. ^ Stich, T. A.; Myers, W. K.; Britt, R. D., "Paramagnetic intermediates generated by radical S-adenosylmethionine (SAM) enzymes", Acc. Chem. Res. 2014, 47, 2235-2243.
  2. ^ Quinone Methides in Lignification
  3. ^ Wang P, Song Y, Zhang L, He H, Zhou X (2005). "Quinone methide derivatives: important intermediates to DNA alkylating and DNA cross-linking actions". Curr Med Chem. 12 (24): 2893–2913. PMID 16305478. doi:10.2174/092986705774454724. 
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  25. ^ Burke Research Group University of Wisconsin
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External links[edit]